tbuckley/cabot-search huggingface dataset:
Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis: 48-week clinical and radiographic results of the investigator-initiated randomised controlled NORD-STAR trial
Authors: Mikkel Østergaard, Ronald F van Vollenhoven, Anna Rudin, Merete Lund Hetland, Marte Schrumpf Heiberg, Dan C Nordström, Michael T Nurmohamed, Bjorn Gudbjornsson, Lykke Midtbøll Ørnbjerg, Pernille Bøyesen, Kristina Lend, Kim Hørslev-Petersen, Till Uhlig, Tuulikki Sokka, Gerdur Grondal, Simon Krabbe, Joakim Lindqvist, Inger Gjertsson, Daniel Glinatsi, Meliha Crnkic Kapetanovic, Anna-Birgitte Aga, Francesca Faustini, Pinja Parmanne, Tove Lorenzen, Cagnotto Giovanni, Johan Back, Oliver Hendricks, Daisy Vedder, Tuomas Rannio, Emma Grenholm, Maud Kristine Ljoså, Eli Brodin, Hanne Lindegaard, Annika Söderbergh, Milad Rizk, Alf Kastbom, Per Larsson, Line Uhrenholt, Søren Andreas Just, David J Stevens, Trine Bay Laurbjerg, Gunnstein Bakland, Inge Christoffer Olsen, Espen A Haavardsholm, Jon Lampa
Journal: Annals of the Rheumatic Diseases (2023)

The optimal first-line treatment in early rheumatoid arthritis (RA) is debated. We compared clinical and radiographic outcomes of active conventional therapy with each of three biological treatments with different modes of action.Investigator-initiated, randomised, blinded-assessor study. Patients with treatment-naïve early RA with moderate-severe disease activity were randomised 1:1:1:1 to methotrexate combined with (1) active conventional therapy: oral prednisolone (tapered quickly, discontinued at week 36) or sulfasalazine, hydroxychloroquine and intra-articular glucocorticoid injections in swollen joints; (2) certolizumab pegol; (3) abatacept or (4) tocilizumab. Coprimary endpoints were week 48 Clinical Disease Activity Index (CDAI) remission (CDAI ≤2.8) and change in radiographic van der Heijde-modified Sharp Score, estimated using logistic regression and analysis of covariance, adjusted for sex, anticitrullinated protein antibody status and country. Bonferroni's and Dunnet's procedures adjusted for multiple testing (significance level: 0.025).Eight hundred and twelve patients were randomised. Adjusted CDAI remission rates at week 48 were: 59.3% (abatacept), 52.3% (certolizumab), 51.9% (tocilizumab) and 39.2% (active conventional therapy). Compared with active conventional therapy, CDAI remission rates were significantly higher for abatacept (adjusted difference +20.1%, p<0.001) and certolizumab (+13.1%, p=0.021), but not for tocilizumab (+12.7%, p=0.030). Key secondary clinical outcomes were consistently better in biological groups. Radiographic progression was low, without group differences.The proportions of patients with serious adverse events were abatacept, 8.3%; certolizumab, 12.4%; tocilizumab, 9.2%; and active conventional therapy, 10.7%.Compared with active conventional therapy, clinical remission rates were superior for abatacept and certolizumab pegol, but not for tocilizumab. Radiographic progression was low and similar between treatments.NCT01491815.
Examining the effect of the COVID-19 pandemic on community virus prevalence and healthcare utilisation reveals that peaks in asthma, COPD and respiratory tract infection occur with the re-emergence of rhino/enterovirus
Authors: Terence Ho, Abdullah Shahzad, Aaron Jones, Natya Raghavan, Mark Loeb, Neil Johnston
Journal: Thorax (2023)

Introduction Airway disease exacerbations are cyclical related to respiratory virus prevalence. The COVID-19 pandemic has been associated with reduced exacerbations possibly related to public health measures and their impact on non-COVID-19 respiratory viruses. We aimed to investigate the prevalence of non-COVID-19 respiratory viruses during the pandemic compared with prior in Ontario, Canada and healthcare utilisation related to asthma, chronic obstructive pulmonary disease (COPD) and respiratory tract infection. Methods This is a population-based retrospective analysis of respiratory virus tests, emergency department (ED) visits and hospitalisations between 2015 and 2021 in Ontario. Weekly virus testing data were used to estimate viral prevalence for all non-COVID-19 respiratory viruses. We plotted the %positivity and observed and expected counts of each virus to visualise the impact of the pandemic. We used Poisson and binomial logistic regression models to estimate the change in %positivity, count of positive viral cases and count of healthcare utilisation during the pandemic. Results The prevalence of all non-COVID-19 respiratory viruses decreased dramatically during the pandemic compared with prior. Comparing periods, the incidence rate ratio (IRR) for positive cases corresponded to a &gt;90% reduction for non-COVID-19 respiratory viruses except adenovirus and rhino/enterovirus. Asthma-related ED visits and hospital admissions fell by 57% (IRR 0.43 (95% CI 0.37 to 0.48)) and 61% (IRR 0.39 (95% CI 0.33 to 0.46)). COPD-related ED visits and admissions fell by 63% (IRR 0.37 (95% CI 0.30 to 0.45)) and 45% (IRR 0.55 (95% CI 0.48 to 0.62)). Respiratory tract infection ED visits and admissions fell by 85% (IRR 0.15 (95% CI 0.10 to 0.22)), and 85% (IRR 0.15 (95% CI 0.09 to 0.24)). Rather than the usual peaks in disease condition, during the pandemic, healthcare utilisation peaked in October when rhino/enterovirus peaked. Conclusions The prevalence of nearly all non-COVID-19 respiratory viruses decreased during the pandemic and was associated with marked reductions in ED visits and hospitalisations. The re-emergence of rhino/enterovirus was associated with increased healthcare utilisation.
Cancer survivors’ health behaviors and outcomes: a population-based study of sexual and gender minorities
Authors: Ulrike Boehmer, Shine Chang, Nelson F Sanchez, Bill M Jesdale, Matthew B Schabath
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Most case-control studies compare cancer survivors with general population controls without considering sexual orientation or gender identity. This case-control analysis compared health risk behaviors and health outcomes among sexual and gender minority cancer survivors to those of matched sexual and gender minority participants without cancer (controls). Methods Using data from the 2014-2021 Behavioral Risk Factor Surveillance System, a population-based sample of 4507 cancer survivors who self-identified as transgender, gay men, bisexual men, lesbian women, or bisexual women were 1:1 propensity score matched, using age at survey, race and ethnicity, marital status, education, access to health care, and US census region. Within each sexual and gender minority group, behaviors and outcomes were compared between survivors and participants without cancer, and survivors’ odds ratios and 95% confidence intervals calculated. Results Gay male survivors had higher odds of depression, poor mental health, limited usual activities, difficulty concentrating, and fair or poor health. Few differences were observed between bisexual male survivors and participants without cancer. Compared with controls, lesbian female survivors had greater odds of overweight–obese status, depression, poor physical health, and fair or poor health. Bisexual female survivors had the highest rates of current smoking, depression, poor mental health, and difficulty concentrating across all sexual and gender minority groups. Statistically significantly different from transgender controls, transgender survivors had greater odds of heavy alcohol use, physical inactivity, and fair or poor health. Conclusions This analysis revealed an urgent need to address the high prevalence of engaging in multiple health risk behaviors and not following guidelines to avoid second cancers, additional adverse outcomes, and cancer recurrences among sexual and gender minority cancer survivors.
Should we prefer biologics over nonbiological agents in psoriasis?
Authors: Sarah E Thomas, Juul M P A van den Reek
Journal: British Journal of Dermatology (2023)

Journal Article Corrected proof Should we prefer biologics over nonbiological agents in psoriasis? Get access Sarah E Thomas, Sarah E Thomas Department of Dermatology, Radboudumc, Nijmegen, the Netherlands https://orcid.org/0000-0002-1343-353X Search for other works by this author on: Oxford Academic Google Scholar Juul M P A van den Reek Juul M P A van den Reek Department of Dermatology, Radboudumc, Nijmegen, the Netherlands Correspondence: Juul M.P.A. van den Reek.Email: juul.vandenreek@radboudumc.nl https://orcid.org/0000-0002-3642-2673 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad231, https://doi.org/10.1093/bjd/ljad231 Published: 09 July 2023 Article history Received: 21 June 2023 Revision received: 26 June 2023 Published: 09 July 2023 Corrected and typeset: 26 July 2023
Supramolecular nanoarchitectonics of phenolic-based nanofiller for controlled diffusion of versatile drugs in hydrogels
Authors: Jiezhou Pan, Haotian Liao, Guidong Gong, Yunxiang He, Qin Wang, Lang Qin, Yaoyao Zhang, Hirotaka Ejima, Blaise L. Tardy, Joseph J. Richardson, Jiaojiao Shang, Orlando J. Rojas, Yong Zeng, Junling Guo
Journal: Journal of Controlled Release (2023)
Mepolizumab for treatment of adolescents and adults with eosinophilic oesophagitis: a multicentre, randomised, double-blind, placebo-controlled clinical trial
Authors: Evan S Dellon, Kathryn A Peterson, Benjamin L Mitlyng, Alina Iuga, Christine E Bookhout, Lindsay M Cortright, Kacie B Walker, Timothy S Gee, Sarah J McGee, Brenderia A Cameron, Joseph A Galanko, John T Woosley, Swathi Eluri, Susan E Moist, Ikuo Hirano
Journal: Gut (2023)

We aimed to determine whether mepolizumab, an anti-IL-5 antibody, was more effective than placebo for improving dysphagia symptoms and decreasing oesophageal eosinophil counts in eosinophilic oesophagitis (EoE).
Cost–utility analysis of tapering strategies of biologicals in rheumatoid arthritis patients in the Netherlands
Authors: Luuk van Esveld, Juul M Cox, T Martijn Kuijper, Tessa M Bosch, Angelique EAM Weel-Koenders
Journal: Annals of the Rheumatic Diseases (2023)

Current guidelines recommend tapering biological disease-modifying antirheumatoid drugs (bDMARDs) in rheumatoid arthritis (RA) if the disease is under control. However, guidelines on tapering are lacking. Assessing cost-effectiveness of different tapering strategies might provide broader input for creating guidelines on how to taper bDMARDs in patients with RA. The aim of this study is to evaluate the long-term cost-effectiveness from a societal perspective of bDMARD tapering strategies in Dutch patients with RA, namely 50% dose reduction (tapering), discontinuation and a 50% dose reduction followed by discontinuation (de-escalation).Using a societal perspective, a Markov model with a life-time horizon of 30 years was used to simulate 3-monthly transitions between Disease Activity 28 (DAS28)-defined health states of remission (<2.6), low disease activity (2.6<DAS28<3.2) and medium-high disease activity (DAS28>3.2). Transition probabilities were estimated through literature search and random effects pooling. Incremental costs, incremental quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs) and incremental net monetary benefits for each tapering strategy were compared with continuation. Deterministic, probabilistic sensitivity analyses and multiple scenario analyses were performed.After 30 years, the ICERs were €115 157/QALY lost, €74 226/QALY lost and €67 137/QALY lost for tapering, de-escalation and discontinuation, respectively; mainly driven by bDMARD cost savings and a 72.8% probability of a loss in quality of life. This corresponds to a 76.1%, 64.3% and 60.1% probability of tapering, de-escalation and discontinuation being cost-effective, provided a willingness-to-accept threshold of €50 000/QALY lost.Based on these analyses, the 50% tapering approach saved the highest cost per QALY lost.
Specificity of polygenic signatures across symptom dimensions in bipolar disorder: an analysis of UK Bipolar Disorder Research Network data
Authors: Judith Allardyce, Alastair G Cardno, Katherine Gordon-Smith, Lisa Jones, Arianna Di Florio, James T R Walters, Peter A Holmans, Nicholas J Craddock, Ian Jones, Michael J Owen, Valentina Escott-Price, Michael C O'Donovan
Journal: The Lancet Psychiatry (2023)

Current definitions and clinical heterogeneity in bipolar disorder are major concerns as they obstruct aetiological research and impede drug development. Therefore, stratification of bipolar disorder is a high priority. To inform stratification, our analysis aimed to examine the patterns and relationships between polygenic liability for bipolar disorder, major depressive disorder (MDD), and schizophrenia with multidimensional symptom representations of bipolar disorder.
Lifetime risk, life expectancy, loss-of-life expectancy and lifetime healthcare expenditure for Stevens–Johnson syndrome/toxic epidermal necrolysis in Taiwan: follow-up of a nationwide cohort from 2008 to 2019
Authors: Ying-Ming Chiu, Hsien-Yi Chiu
Journal: British Journal of Dermatology (2023)

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) not only cause acute, devastating mucocutaneous reactions but also have long-lasting implications on survivors' lives.To quantify the lifetime burden of SJS/TEN.The cumulative incidence rate (CIR), life expectancy (LE), loss-of-life expectancy (LoLE) and lifetime healthcare expenditure (HE) for SJS/TEN were estimated over the period from 2008 to 2019 using data from the National Health Insurance Research Database of Taiwan and life tables of vital statistics.In this nationwide cohort of 6552 incident SJS/TEN cases, a trend towards a decrease in the CIR was observed between 2008 and 2019. Compared with the general population, patients with SJS/TEN experience a tremendous loss of 9.43 (1.06) [mean (SEM)] years of LE after diagnosis of SJS/TEN. Male patients with SJS/TEN had higher LoLE [10.74 (1.22) vs. 7.69 (1.43) years] and annual HE than females. Younger age at diagnosis of SJS/TEN was associated with longer LE but greater LoLE and higher lifetime HE. Patients with intensive care unit admission on diagnosis, malignancy, diabetes mellitus, end-stage renal disease and SJS/TEN-associated sequelae experienced substantially greater LoLE and HE per life year.Patients with SJS/TEN suffer substantial loss-of-LE and HE, particularly young patients, compared with the general population. These data provide a reference estimate of the lifetime burden of SJS/TEN to help health authorities evaluate the cost-effectiveness of future preventive and treatment strategies to minimize the burden of SJS/TEN.
Modelling speed reduction behaviour on variable speed limit-controlled highways considering surrounding traffic pressure: A random parameters duration modelling approach
Authors: Yasir Ali, Mark P.H. Raadsen, Michiel C.J. Bliemer
Journal: Analytic Methods in Accident Research (2023)

Variable speed limits are frequently used to improve traffic safety and harmonise traffic flow. This study investigates how, and to what extent, drivers reduce their speed upon passing a variable speed limit sign. We specifically consider the impact on braking behaviour due to the systematic inclusion of different social pressures exerted by surrounding traffic. This social pressure is the natural result of having two vehicle cohorts created by a change in the variable speed limit (the new speed limit being higher than the original). The cohort with the higher speed limit overtakes vehicles with the lower speed limit, instigating a specific passing rate on drivers in the lower speed cohort. A driving simulator study is employed to obtain individual driver data whilst being able to systematically change the social pressure applied. A sample comprising sixty-seven participants conducted multiple randomised drives, with varying passing rates from as low as 90 veh/h to as high as 360 veh/h. The speed reduction behaviour of the participants is modelled using a random parameter duration modelling approach. Both the panel nature of the data and unobserved heterogeneity are captured through a correlated grouped random parameters with heterogeneity-in-the-mean model. The random parameters are predicated on the different passing rate scenarios, allowing drivers to take shorter or longer to reduce their speeds compared to the reference passing rate. It is shown that the extent of social pressure impacts braking behaviour and therefore affects safety measures, which is a function of the magnitude of the speed limit change. In addition, an extensive decision tree analysis is conducted to understand differential braking behaviour. Results reveal that, on average, female drivers take a shorter time to reduce their speed under a high passing rate but longer in a low passing rate scenario compared to males. Similarly, young drivers are found to take longer to reduce their speeds in a high passing rate scenario compared to other age groups. Our main findings indicate that the within-cohort safety is lowest under low passing rates due to comparatively larger speed differences between drivers. Yet, under a high passing rate, we observe an increase in violation of the speed limit by the lower speed limit vehicles (but less within cohort speed differences). Whilst normally this would be an undesired effect across cohorts, this violation is argued to lead to increased safety due to the smaller discrepancy in speed.
Prostaglandin E1 infants with ductus arteriosus-dependent congenital heart disease.
Authors: M D Freed, M A Heymann, A B Lewis, S L Roehl, R C Kensey
Journal: Circulation (1981)

infants with ductus arteriosus-dependent con- genital heart disease (385 cyanotic and 107 acyanotic) received prostaglandin E, (PGE,) in 56 centers in the United States as part of a protocol sponsored by the Upjohn Company.In the infants with cyanotic congenital heart disease, the mean Pao2 for the group increased from 26.7 mm Hg before to 38.5 mm Hg during infusion (p < 0.001).Infants older than age 4 days had a higher preinfusion Pao2 and a smaller increase in Pao2.In- fants weighing more than 4 kg at birth and alkalotic infants (pH > 7.45) had a smaller increase in Pao2.No differences in response were found with respect to mode of administration (intra-arterial or i.v.), gender, maternal age, or preinfusion Paco2.PGE, provides excellent palliation for infants with ductus arte- riosus-dependent cyanotic congenital heart disease.Of the 107 infants with acyanotic congenital heart disease, 46 had juxtaductal coarctation and 34 had in- terruption of the aortic arch.Clinical improvement occurred in about 80% in each group.In the infants with aortic interruption, descending aortic blood pressures increased and the pressure differences across the ductus arteriosus decreased markedly.In the infants with coarctation, descending aortic blood pressures increased and ascending aortic pressure decreased.The systolic pressure difference across the coarctation decreased markedly, from 45 to 9 mm Hg.Infants in whom the ductus arteriosus was closed before the infusion showed no beneficial effects.In infants in whom a constricted ductus arteriosus relaxed, the effect occurred more slowly than in infants with cyanotic heart disease.PGE, also provides excellent palliation in infants with aortic obstruction in which lower body perfusion is dependent on the ductus arteriosus.
Inflammatory and tolerogenic myeloid cells determine outcome following human allergen challenge
Authors: Astrid L. Voskamp, Tamar Tak, Maarten L. Gerdes, Roberta Menafra, Ellen Duijster, Simon P. Jochems, Szymon M. Kielbasa, Tom Groot Kormelink, Koen A. Stam, Oscar R.J. van Hengel, Nicolette W. de Jong, Rudi W. Hendriks, Susan L. Kloet, Maria Yazdanbakhsh, Esther C. de Jong, Roy Gerth van Wijk, Hermelijn H. Smits
Journal: The Journal of Experimental Medicine (2023)

Innate mononuclear phagocytic system (MPS) cells preserve mucosal immune homeostasis. We investigated their role at nasal mucosa following allergen challenge with house dust mite. We combined single-cell proteome and transcriptome profiling on nasal immune cells from nasal biopsies cells from 30 allergic rhinitis and 27 non-allergic subjects before and after repeated nasal allergen challenge. Biopsies of patients showed infiltrating inflammatory HLA-DRhi/CD14+ and CD16+ monocytes and proallergic transcriptional changes in resident CD1C+/CD1A+ conventional dendritic cells (cDC)2 following challenge. In contrast, non-allergic individuals displayed distinct innate MPS responses to allergen challenge: predominant infiltration of myeloid-derived suppressor cells (MDSC: HLA-DRlow/CD14+ monocytes) and cDC2 expressing inhibitory/tolerogenic transcripts. These divergent patterns were confirmed in ex vivo stimulated MPS nasal biopsy cells. Thus, we identified not only MPS cell clusters involved in airway allergic inflammation but also highlight novel roles for non-inflammatory innate MPS responses by MDSC to allergens in non-allergic individuals. Future therapies should address MDSC activity as treatment for inflammatory airway diseases.
The interleukin-1 pathway as a treatment target in early-stage hidradenitis suppurativa?
Authors: Ina Suhrkamp, Sascha Gerdes
Journal: British Journal of Dermatology (2023)

Journal Article Corrected proof The interleukin-1 pathway as a treatment target in early-stage hidradenitis suppurativa? Get access Ina Suhrkamp, Ina Suhrkamp Department of Dermatology, Venereology and Allergology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany Correspondence: Ina Suhrkamp. Email: i.suhrkamp@dermatology.uni-kiel.de https://orcid.org/0000-0002-3270-4884 Search for other works by this author on: Oxford Academic Google Scholar Sascha Gerdes Sascha Gerdes Department of Dermatology, Venereology and Allergology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany https://orcid.org/0000-0002-6667-7757 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad225, https://doi.org/10.1093/bjd/ljad225 Published: 10 July 2023 Article history Received: 24 June 2023 Published: 10 July 2023 Corrected and typeset: 28 July 2023
Q&amp;A: Philip Greenberg on T Cells, IO's Future
Journal: Cancer Discovery (2023)

Abstract Philip Greenberg, MD, assumed a 1-year term as president of the American Association for Cancer Research in April 2023. In this interview, he highlighted some tenure priorities, including improving scientists’ ability to communicate with the public, and discussed his own research on T-cell receptor therapies, as well as the upcoming decade for immuno-oncology.
Macrophage-reprogramming upconverting nanoparticles for enhanced TAM-mediated antitumor therapy of hypoxic breast cancer
Authors: Johyun Yoon, Xuan Thien Le, Juho Kim, Hyunjun Lee, Nguyen Thi Nguyen, Woo Tak Lee, Eun Seong Lee, Kyung Taek Oh, Han-Gon Choi, Yu Seok Youn
Journal: Journal of Controlled Release (2023)